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Randomized Controlled Trial
. 2023 Nov:194:113324.
doi: 10.1016/j.ejca.2023.113324. Epub 2023 Sep 7.

Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE randomized clinical trial

Marcus Schmidt  1 , Ulrike Nitz  2 , Toralf Reimer  3 , Sabine Schmatloch  4 , Heiko Graf  5 , Marianne Just  6 , Elmar Stickeler  7 , Michael Untch  8 , Ingo Runnebaum  9 , Antje Belau  10 , Jens Huober  11 , Christian Jackisch  12 , Manfred Hofmann  13 , Jutta Krocker  14 , Valentina Nekljudova  15 , Sibylle Loibl  16 ; GBG/AGO-B, NOGGO/WSG study groups
Affiliations
Randomized Controlled Trial

Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE randomized clinical trial

Marcus Schmidt et al. Eur J Cancer. 2023 Nov.

Abstract

Aim of the study: Evaluation of the impact of a de-escaleted chemotherapy regimen consisting of capecitabine (Cap) on invasive disease-free survival (iDFS) in patients ≥65 years with node-positive/high-risk node-negative early breast cancer (BC) receiving ibandronate (Ib).

Methods: ICE (Ib with or without Cap in Elderly patients with early breast cancer) was a multicentre phase 3 clinical trial with a 2020 update of long-term follow-up for overall survival enroling node-positive/high-risk node-negative patients ≥65 years with early BC. Patients were randomised to Cap 2000 mg/m² day 1-14 q3w for 6 cycles plus Ib (50 mg p.o. daily or alternatively 6 mg intravenous q4w) or Ib alone for 2 years. Endocrine therapy was recommended for hormone receptor (HR)-positive patients. The primary endpoint was iDFS analysed using Cox proportional hazards regression and log-rank analysis.

Results: 1358 (96.4%) of 1409 randomised patients started treatment. 564 (83.4%) completed 6 cycles of Cap. 513 (77.7%) and 516 (78.8%) completed Ib in the Cap+Ib and Ib alone arm, respectively. Median age was 71 (range 64-88) years, 1099 (81%) were HR-positive, 705 (51.9%) node-negative. At a median follow-up of 61.3 months, 5-year iDFS was 78.8% for Cap+Ib versus 75.0% for Ib alone (p = 0.80). Effects were independent of age, nodal, and HR status. The addition of Cap caused significantly higher skin and gastrointestinal toxicity.

Conclusions: The adjuvant combination of Cap+Ib did not show significantly better iDFS than Ib alone in node-positive/high-risk node-negative older BC patients, of whom HR-positive patients were also treated with endocrine therapy.

Trial registration: Study in elderly patients with early breast cancer (ICE), NCT00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859.

Keywords: Adjuvant therapy; Breast cancer; Capecitabine; Clinical trial; Ibandronate.

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Conflict of interest statement

Declaration of Competing Interest M. Schmidt reports personal fees from AstraZeneca, personal fees from BioNTech, personal fees from Daiichi Sankyo, personal fees from Eisai, peronal fees from Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Pierre-Fabre, personal fees from Roche, and personal fees from SeaGen outside the submitted work; in addition, M. Schmidt has a patent for EP 2390370 B1: A method for predicting the response of a tumour in a patient suffering from or at risk of developing recurrent gynaecologic cancer towards a chemotherapeutic agent issued and a patent for EP 2951317 B1: A method for predicting the benefit from inclusion of a taxane in a chemotherapy regimen in patients with breast cancer issued. S. Loibl reports grants or contracts paid to institute from Abbvie, AstraZeneca, DSI, Celgene, Gilead, Novartis, Pfizer, Roche, Molecular H; in addition, S. Loibl has royalties or licences for Digital Ki67 Evaluator from VM Scope GmbH that were paid to institute; in addition, S. Loibl receives honorary for lectures paid to the institute from AstraZeneca, DSI, Gilead, Novartis, Pfizer, and Roche; non-financial for Medical Writing from DSI, Gilead, Novartis, Pfizer, Roche, and Seagen; in addition, S. Loibl has patent for EP14153692.0, EP21152186.9, EP15702464.7 and EP19808852.8, all patents via institute; in addition, S. Loibl declares participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, Eisai Europe, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Relay Therapeutics, Roche, Sanofi, and Seagen, all paid to institute. C. Jakisch reports consulting fees from Novartis, Roche, Celgene, Pfizer, Lilly, and Exact Sciences; in addition, C. Jakisch declares support for attending meetings and/or travel from Novartis, Roche, Celgene, Pfizer, Lilly, and Exact Sciences. J. Huober reports grants or contracts paid to institute from Celgene, Novartis, Hexal, and Lilly; in addition, J. Huober declares consulting fees from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie, Seagen, and Gilead; in addition, J. Huober receives payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie, Seagen, and Gilead; in addition, J. Huober reports support for attending meetings and/or travel from Roche, Pfizer, Novartis, Celgene, Daiichi, and Gilead. M. Untch reports support for the present manuscript from GBG, financial and drug support from AstraZeneca, and financial and drug support from Roche; in addition, M. Untch receives consulting fees to the institution from AstraZeneca, Roche, Pfizer, Novartis, Sanofi Aventis, Daiichi Sankyo, Pierre Fabre, Gilead, Seagen, Amgen, Lilly, and MSD; in addition, M. Untch reports payment for lectures to the institution from AstraZeneca, Roche, Pfizer, Novartis, Sanofi Aventis, Daiichi Sankyo, Pierre Fabre, Gilead, Seagen, Amgen, Lilly, and MSD; in addition, M. Untch declares support for attending meetings and/or travel within the bounds of speakers or expert agreement. V. Nekljudova declares to be GBG Forschungs GmbH employee. GBG Forschungs GmbH received funding for research grants from Abbvie, AstraZeneca, BMS, Daiichi-Sankyo, Gilead, Novartis, Pfizer and Roche (paid to the institution); other (non-financial/medical writing) from Daiichi-Sankyo, Gilead, Novartis, Pfizer, Roche and Seagen (paid to the institution). GBG Forschungs GmbH has following royalties/patents: EP14153692.0, EP21152186.9, EP15702464.7, EP19808852.8 and VM Scope GmbH. A. Belau, H. Graf, M. Hofmann, M. Just, J. Krocker, U. Nitz, I. Runnebaum, and E. Stickeler report no disclosures. No other potential conflict of interest relevant to this article was reported.

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